We have tested Jerne's hypothesis (9) that the phenomenon alloreactivity is explained by the existence of T cells that express germline-encoded receptors specific for major histocompatibility complex antigens and that these cells undergo no change in specificity during thymic differentiation. T cells from [F1 leads to Parent] bone marrow radiation chimeras reactive to conventional antigens are known to have a self preference, i.e., [A X B leads to A] chimeras respond better to H-2A-plus-antigen than to H-2B-plus-antigen. We show here that alloreactive cells from such chimeras also have a self preference. Thus, H-2k-specific alloreactive T cells from [H-2b X H-2d leads to H-2b] and [H-2b X H-2d leads to H-2d] chimeras cross-react more on TNP-modified H-2b or H-2d targets, respectively. In contrast to Jerne's prediction, the results suggest that the receptor repertoire of alloreactive F1 cells is influenced by H-2 antigens on radiation-resistant cells present during T cell ontogeny. By this criterion of having a self preference in H-2 restriction, alloreactive T cells appear to be similar to T cells that respond to conventional antigens.